Antiangiogenic therapy and tumor progression

Cancer Cell. 2004 Jan;5(1):13-7. doi: 10.1016/s1535-6108(03)00336-2.


Angiogenesis is necessary for tumor growth (a rationale for antiangiogenic therapy), but hypoxia caused by such a therapy will, in theory, drive tumor progression and metastasis. To reconcile conflicting notions, we discuss that, first, although a shift from normoxia (21% O2) to hypoxia indeed activates cancer cells for aggressive behavior, this may not occur during therapy, because most cancers are not normoxic to start with. Second, only successful antiangiogenic therapy, which is capable of controlling cancer, will select for resistance and progression. After all, in order to occur, therapy-induced tumor progression must be preceded by tumor regression.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Apoptosis / physiology
  • Endothelial Cells / metabolism*
  • Epithelial Cells / metabolism*
  • Humans
  • Hypoxia / physiopathology
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inhibitors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transcription Factors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A